Active intermediates formed in the metabolic activation of procarbazine will be investigated using synthesized metabolites and deuterium labeled variants. Activation pathways will be related to the carcinogen 1, 2-dimethylhydrazine. Metabolism of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DIC) and the closely related carcinogen 3,3-dimethyl-1-phenyltriazene will be studied in vitro and in vivo using high performance liquid chromatography and chemical ionization mass spectrometry techniques. Nucleophilic susceptibility and proton exchange of the methylating species generated from these compounds and dimethyl-N-nitrosamine and N-methyl-N-nitrosourea will be compared to determine whether identical intermediates have been generated. The diverse biological effects of these agents may be related to different properties or distribution of the respective chemically activated precursors to the ultimate methylating agent. The half-life of these metabolically generated precursors will be measured.